Parent-therapist partnership to ELEVATE gross motor function in children with perinatal stroke: protocol for a mixed methods randomized controlled trial.

BACKGROUND: There is increasing evidence for early, active rehabilitation to enhance motor function following early brain injury. This is clear for interventions targeting the upper extremity, whereas passive treatment approaches for the lower extremity persist. The purpose of this trial is to evaluate the effectiveness of early, intensive rehabilitation targeting the lower extremity and delivered in a parent-therapist partnership model for children with perinatal stroke. METHODS: We describe a protocol for a waitlist-control, single-blind, mixed methods effectiveness randomized controlled trial, with an embedded qualitative study using interpretative description. Participants are children with perinatal stroke aged eight months to three years with signs of hemiparesis. Participants will be randomly allocated to an immediate ELEVATE (Engaging the Lower Extremity Via Active Therapy Early) intervention group, or a waitlist-control group, who will receive usual care for six months. The ELEVATE intervention involves one hour of training four days per week for 12 weeks, with a pediatric therapist and a parent or guardian each delivering two sessions per week. The intervention targets the affected lower extremity by progressively challenging the child while standing and walking. The primary outcome measure is the Gross Motor Function Measure-66. Secondary outcomes include the Pediatric Quality of Life Inventory™, Young Children's Participation and Environment Measure, and an instrumented measure of spasticity. A cost-effectiveness analysis and qualitative component will explore benefit to costs ratios and parents' perspectives of early, intensive rehabilitation, and their role as a partner in the rehabilitation, respectively. DISCUSSION: This study has the potential to change current rehabilitation for young children with perinatal stroke if the ELEVATE intervention is effective. The parent interviews will provide further insight into benefits and challenges of a partnership model of rehabilitation. The mixed methods design will enable optimization for transfer of this collaborative approach into physical therapy practice. TRIAL REGISTRATION: ClinicalTrials.gov NCT03672864 . Registered 17 September 2018.

The differential associative relationship between early risk factors, neonatal morbidities and early neurodevelopmental outcome in preterm infants <29 weeks' gestation.

BACKGROUND: Very preterm infants of <29 weeks' gestation are at high risk for adverse neurodevelopment due to multiple risk factors in the early stages of life. There is little information regarding the associative effects of risk factors in early life, neonatal morbidities and subsequent neurodevelopmental outcomes. AIMS: Investigate the association of early neurodevelopmental outcomes, neonatal complications and the risk factors in the early hours of life in a cohort of preterm infants <29 weeks' gestational age. METHODS: We enrolled all surviving preterm neonates born at gestation <29 weeks between January 2015 and June 2021 in the University of Hong Kong-Shenzhen Hospital. Demographic and clinical characteristics were collected from a database of the neonatal intensive care unit. Neurodevelopmental outcomes of the survivors were evaluated using the Ages and Stages Questionnaire (ASQ-3) which were measured at the adjusted age of 12 to 18 months. The multivariate linear regression model was used to determine correlation presented as ß coefficient (ß) with 95 % confidence intervals (CI). RESULTS: In this cohort of 56 survivors <29 weeks' gestation, urine output within the first 12 h of life and Apgar score at 5 min were positively associated with different domains of ASQ-3 score, however male sex and highest fraction of inspired oxygen (FiO2) in the first 12 h of life were negatively related with at least one of neurocognitive domains of ASQ-3 at adjusted age of 12 to 18 months. During hospitalization, in addition to the frequency of packed red cell transfusions, the development of severe necrotizing enterocolitis was inversely associated with both neuromotor and neurocognitive skills (gross motor domain: ß = -16.93, CI: -32.04, -1.82; fine motor domain: ß = -16.42, CI: -28.82, -4.02; problem solving domain: ß = -13.14, CI: -24.45, -1.83; all P < 0.05), whereas severe intraventricular hemorrhage had adverse effects on gross motor only (ß = -13.04, CI: -24.42, -1.65; P = 0.03). Bronchopulmonary dysplasia and retinopathy of prematurity were not related with ASQ-3. CONCLUSIONS: In this small cohort study of very preterm neonates born at <29 weeks' gestation, risk factors in the early hours of life and neonatal morbidities during hospitalization had differential associative relationships with ASQ-3 at 12-18 months adjusted age. This information may be important for parental counseling and management including early diagnosis and intervention.

A Family-Centered, Multidisciplinary Clinic for Early Diagnosis of Neurodevelopmental Impairment and Cerebral Palsy in China-A Pilot Observation.

Background: Comprehensive multidisciplinary assessment of neurodevelopmental outcomes of high-risk neonates may have significant challenges in low- and middle-income countries, in addition to socio-cultural barriers. We aimed to compare the time to diagnosis of neurodevelopmental impairment (NDI) and cerebral palsy (CP) in preterm neonates (<29 weeks) at a multidisciplinary assessment and care (MDAC) clinic with that of a conventional high-risk infant follow-up clinic in China. Methods: All eligible surviving very preterm neonates born at <29 weeks gestation at the University of Hong Kong-Shenzhen Hospital between January 2015 and December 2019 were followed up in conventional (2015-2017) and MDAC (2018-2020) clinics up to 2 years corrected age with clinical demographic information collected in a prospective database. The MDAC team used standardized developmental assessments. The rates and timing of diagnosing NDI and CP in two epochs were compared. Results: The rates of NDI and CP were not different in two epochs [NDI: 12 (50%) vs. 12 (41%); CP: 3 (12%) vs. 2 (7%) of 24 and 29 surviving infants assessed in conventional and MDAC clinics, respectively]. Infants in the MDAC clinic were diagnosed with NDI and CP earlier than those in the pre-MDAC epoch (6 vs. 14 months corrected age, respectively, P < 0.05). Conclusion: High-risk preterm neonates can be followed more effectively in a family-centered, child-friendly multidisciplinary clinic, leading to an earlier diagnosis of NDI and CP. Early counseling and interventions could be implemented accordingly.

Early, Intensive, Lower Extremity Rehabilitation Shows Preliminary Efficacy After Perinatal Stroke: Results of a Pilot Randomized Controlled Trial.

BACKGROUND: Perinatal stroke injures motor regions of the brain, compromising movement for life. Early, intensive, active interventions for the upper extremity are efficacious, but interventions for the lower extremity remain understudied. OBJECTIVE: To determine the feasibility and potential efficacy of ELEVATE-Engaging the Lower Extremity Via Active Therapy Early-on gross motor function. METHODS: We conducted a single-blind, two-arm, randomized controlled trial (RCT), with the Immediate Group receiving the intervention while the Delay Group served as a 3-month waitlist control. A separate cohort living beyond commuting distance was trained by their parents with guidance from physical therapists. Participants were 8 months to 3 years old, with MRI-confirmed perinatal ischemic stroke and early signs of hemiparesis. The intervention was play-based, focused on weight-bearing, balance and walking for 1 hour/day, 4 days/week for 12 weeks. The primary outcome was the Gross Motor Function Measure-66 (GMFM-66). Secondary outcomes included steps and gait analyses. Final follow-up occurred at age 4. RESULTS: Thirty-four children participated (25 RCT, 9 Parent-trained). The improvement in GMFM-66 over 12 weeks was greater for the Immediate than the Delay Group in the RCT (average change 3.4 units higher) and greater in younger children. Average step counts reached 1370-3750 steps/session in the last week of training for all children. Parent-trained children also improved but with greater variability. CONCLUSIONS: Early, activity-intensive lower extremity therapy for young children with perinatal stroke is feasible and improves gross motor function in the short term. Longer term improvement may require additional bouts of intervention. CLINICAL TRIAL REGISTRATION: This study was registered at ClinicalTrials.gov (NCT01773369).

Outcomes for the extremely premature infant: what is new? And where are we going?

Two approaches were taken to determine what is new and where we are going in terms of outcomes for the extremely premature infant: publications from 2004 to 2007 were reviewed, and the 30-year outcome at the authors' institutions was assessed. Recent literature documents improving early childhood outcomes in the face of improved survival. Childhood cerebral palsy prevalence rates have been reported to be as low as 19 per 1000 live births for infants born at 20-27 weeks gestation. Vision and hearing loss have been reported in fewer than 1% of survivors. The rate of overall intellectual impairment has not improved, although impairment was reduced in a recent trial of caffeine therapy for apnea of prematurity, and this remains an important area for study. In sum, recent findings herald a more positive perspective on the outcome for extremely premature survivors. It can thus be expected that new intensive-care trials will attempt to reduce the proportion of survivors with adverse outcomes. Childhood assessments will have a greater focus on function and participation. Information on improved outcomes for preterm infants will inform guidelines of decision making used to help parents to determine what is best for their child. The audit component of follow-up studies will expand and more cohort and trial studies will become multicenter, national, and international.

Changes in the prevalence of cerebral palsy for children born very prematurely within a population-based program over 30 years.

CONTEXT: Although cerebral palsy (CP) among extremely premature infants has been reported as a major morbidity outcome, there are difficulties comparing published CP rates from many sites over various birth years. OBJECTIVE: To assess the changes in population-based, gestational age-specific prevalence rates of CP among extremely premature infants over 30 years. DESIGN: Prospective population-based longitudinal outcome study. SETTING AND PARTICIPANTS: In Northern Alberta, 2318 infants 20 to 27 weeks' gestational age with birth weights of 500 to 1249 g were liveborn from 1974 through 2003. By 2 years of age, 1437 (62%) had died, 23 (1%) were lost to follow-up, and 858 (37%) had received multidisciplinary neurodevelopmental assessment. MAIN OUTCOME MEASURE: Population-based prevalence rates of CP were determined. Logistic regression with linear spline was used to assess changes in CP prevalence over time. RESULTS: At age 2 years, 122 (14.2%) of 858 survivors had CP. This diagnosis was confirmed for each child by age 3 years or older. Among those whose gestational age was 20 to 25 weeks, population-based survival increased from 4% to 31% (P<.001), while CP prevalence per 1000 live births increased monotonically from 0 to 110 until the years 1992-1994 (P<.001) and decreased thereafter to 22 in the years 2001-2003 (P<.001). Among those whose gestational age was 26 to 27 weeks, population-based survival increased from 23% to between 75% and 80% (P<.001), while CP prevalence per 1000 live births increased monotonically from 15 to 155 until the years 1992-1994 (P<.001) and then decreased to 16 in the years 2001-2003 (P<.001). For all survivors born in the years 2001-2003, CP prevalence was 19 per 1000 live births. CONCLUSION: Population-based CP prevalence rates for children whose gestational age was 20 to 27 weeks and whose birth weight ranged from 500 to 1249 g show steady reductions in the last decade with stable or reducing mortality, reversing trends prior to 1992-1994.

Early Intensive Leg Training to Enhance Walking in Children With Perinatal Stroke: Protocol for a Randomized Controlled Trial.

BACKGROUND: Development of motor pathways is modulated by activity in these pathways, when they are maturing (ie, critical period). Perinatal stroke injures motor pathways, including the corticospinal tracts, reducing their activity and impairing motor function. Current intervention for the lower limb emphasizes passive approaches (stretching, braces, botulinum toxin injections). The study hypothesis was that intensive, early, child-initiated activity during the critical period will enhance connectivity of motor pathways to the legs and improve motor function. OBJECTIVE: The study objective was to determine whether early intervention with intensive activity is better than standard care, intervention delivered during the proposed critical period is better than after, and the outcomes are different when the intervention is delivered by a physical therapist in an institution vs. a parent at home. DESIGN: A prospective, delay-group, single-blind, randomized controlled trial (RCT) and a parallel, cohort study of children living beyond commuting distance and receiving an intervention delivered by their parent. SETTING: The RCT intervention was provided in university laboratories, and parent training was provided in the childs home. PARTICIPANTS: Children 8 months to 3 years old with MRI-confirmed perinatal ischemic stroke and early signs of hemiparesis. INTERVENTION: Intensive, play-based leg activity with weights for the affected leg and foot, 1 hour/day, 4 days/week for 12 weeks. MEASUREMENTS: The primary outcome was the Gross Motor Function Measure-66 score. Secondary outcomes were motion analysis of walking, full-day step counts, motor evoked potentials from transcranial magnetic stimulation, and patellar tendon reflexes. LIMITATIONS: Inter-individual heterogeneity in the severity of the stroke and behavioral differences are substantial but measurable. Differences in intervention delivery and assessment scoring are minimized by standardization and training. CONCLUSIONS: The intervention, contrary to current practice, could change physical therapy interventions for children with perinatal stroke.

Chronic Neuromotor Disability After Complex Cardiac Surgery in Early Life.

BACKGROUND AND OBJECTIVES: Little is known about chronic neuromotor disability (CND) including cerebral palsy and motor impairments after acquired brain injury in children surviving early complex cardiac surgery (CCS). We sought to determine the frequency and presentation of CND in this population while exploring potentially modifiable acute care predictors. METHODS: This prospective follow-up study included 549 children after CCS requiring cardiopulmonary bypass at ≤6 weeks of age. Groups included those with only 1 CCS, mostly biventricular CHD, and those with >1 CCS, predominantly single ventricle defects. At 4.5 years of age, 420 (94.6%) children received multidisciplinary assessment. Frequency of CND is given as percentage of assessed survivors. Predictors of CND were analyzed using multiple logistic regression analysis. RESULTS: CND occurred in 6% (95% confidence interval [CI] 3.7%-8.2%) of 4.5-year survivors; for 1 CCS, 4.2% (CI 2.3%-6.1%) and >1, 9.8% (CI 7%-12.6%). CND presentation showed: hemiparesis, 72%; spasticity, 80%; ambulation, 72%; intellectual disability, 44%; autism, 16%; epilepsy, 12%; permanent vision and hearing impairment, 12% and 8%, respectively. Overall, 32% of presumed causative events happened before first CCS. Independent odds ratio for CND are age (days) at first CCS, 1.08 (CI 1.04-1.12; P < .001); highest plasma lactate before first CCS (mmol/L), 1.13 (CI 1.03-1.23; P = 0.008); and >1 CCS, 3.57 (CI 1.48-8.9; P = .005). CONCLUSIONS: CND is not uncommon among CCS survivors. The frequency of associated disabilities characterized in this study informs pediatricians caring for this vulnerable population. Shortening the waiting period and reducing preoperative plasma lactate levels at first CCS may assist in reducing the frequency of CND.